Application of green chemistry in decreasing adverse effect of (R,S)-ibuprofen

Lipases from Candida rugosa (OF and MY) were tested for their application in the enzymatic kinetic resolution of (R,S)-ibuprofen by enantioselective esterification. In this study, screening of enzymes was performed, and lipase MY was selected as an optimal catalyst, which allows to obtain products with high enantiopurity. Additionally, the influence of reaction time on the enantiomeric ratio and conversion was tested. High values of enantiomeric ratio (E in the range of 40.1–71.3) of the esterification of (R,S)- -ibuprofen were obtained using lipase MY, which has a great significance in the field of pharmaceutical synthesis of drugs. The chiral compounds (substrates and products) were analysed with the use of chiral stationary phases. As a result of the optimization, the reaction performed with the application of lipase MY allowed to achieve less toxic for human health (S)-enantiomer of ibuprofen with the high enantiomeric excess of product eep = 95%. Conversion of the reaction was c = 30.6% and enantioselectivity E = 58.9 after 126 h of incubation

A Novel Model of Protein Crystal Growth: Kinetic Limits, Length Scales and the Role of the Double Layer

A kinetic model has been designed that tries to capture some most important physico-chemical properties of crystallization from water-based electrolyte. The crystal growing process is thought to proceed in a conserved system, in which the charged-mass conservation law is obeyed. Although the model phenomenon under study proceeds in a mass-convection regime, it is readily interface-controlled. The interfacial control is identified with the role played by the double-layer, presumably of the Stern type, surrounding the object under growth. The product of supersaturation and individual biomolecule velocity in the double-layer appears to be both the controlling kinetic factor and the asymptotic (kinetic) limit being achieved by the process, i.e. the crystal growth rate approaches the value of the mentioned product. The first successful test of the model was carried out on data representing the lyzosyme crystal growth

A Novel Model of Protein Crystal Growth: Kinetic Limits, Length Scales and the Role of the Double Layer

A kinetic model has been designed that tries to capture some most important physico-chemical properties of crystallization from water-based electrolyte. The crystal growing process is thought to proceed in a conserved system, in which the charged-mass conservation law is obeyed. Although the model phenomenon under study proceeds in a mass-convection regime, it is readily interface-controlled. The interfacial control is identified with the role played by the double-layer, presumably of the Stern type, surrounding the object under growth. The product of supersaturation and individual biomolecule velocity in the double-layer appears to be both the controlling kinetic factor and the asymptotic (kinetic) limit being achieved by the process, i.e. the crystal growth rate approaches the value of the mentioned product. The first successful test of the model was carried out on data representing the lyzosyme crystal growth

Metabolic chiral inversion of 2-arylpropionic acid derivatives (profens)

2-arylpropionic acid derivatives (profens) are one of the most popular anti-inflammatory, analgesic, and antipyretic drugs. They belong to a group of nonsteroidal anti-inflammatory drugs (NSAID) and exhibit metabolic chiral inversion. Enantiomers of these chiral drugs are often characterised by different pharmacological activity. It is estimated that the values of metabolic chiral inversion of (R)-ibuprofen in humans are between 35 and 70%, depending on the condition of the liver and the intake of other medicines, while (R)-flurbiprofen undergoes chiral metabolic inversion to its opposed (S) form only in small range. The described phenomenon in the case of (R)-ketoprofen is limited to a maximum of around 10%. The metabolic chiral inversion is associated with potentially important pharmacotherapeutic and toxicological consequences, and so an attempt was made to analyse this phenomenon for the most commonly used drugs from the profens group

Immobilization of Candida rugosa lipase onto magnetic beads for kinetic resolution of (R,S)-ibuprofen

Two commercially available lipases from Candida rugosa (CRL from Sigma-Aldrich Co. and OF from Meito Sangyo Co.) were immobilized onto glutaraldehyde-activated and EDC/sulfo-NHS-activated amineterminated magnetic beads (MB). In this study a procedure for immobilization of lipase OF using EDC sulfo-NHS onto the surface of magnetic particles was developed. The resulting “OF lipase enzymatic system” yielded good results of enantioselectivity (E=19, eep=83%) and conversion (c=42%) of the kinetic resolution of (R,S)-ibuprofen. Additionally, this procedure provides easy recovery and effective reuse of lipase OF, maintaining the enantioselectivity of the reaction on the same high level after five cycles. It was also demonstrated that the cross-linking reaction of lipases (CRL and OF) via glutaraldehyde onto magnetic support did not result in acceptable levels of conversion and enantioselectivity of the esterification reaction. Based on the results it should be noted that the immobilization technique we studied using EDC and sulfo-NHS onto MB could be potentially important for industrial application of kinetic resolution of non-steroidal anti-inflammatory drugs

Evolution of PAH Features from Proto- to Planetary Nebulae

With the aim to investigate the overall evolution of UIR band features with hardening of UV radiation (increase of the star's effective temperature) we have analysed ISO spectra for 32 C-rich stars: 20 proto-planetary nebulae and 12 planetary nebulae with Wolf-Rayet central stars. In this contribution we discuss variations in the peak position of UIR bands among analysed objects, and demonstrate that variations in the ``7.7'' to 11.3 microns flux ratio are correlated with the effective temperature (probably due to an increase of the ionization state of their carriers).Comment: 4 pages, 3 figures, 1 table, to appear in the Proceedings of the conference "Planetary Nebulae as Astronomical Tools", edited by R. Szczerba, G. Stasi\'nska, and S. K. G\'orny, AIP Conference Proceedings, Melville, New Yor

Application of Lipases from Candida rugosa in the Enantioselective Esterification of (R, S)-Ibuprofen

Three commercially available lipases from Candida rugosa (OF and MY from Meito Sangyo Co., and CRL from Sigma-Aldrich Co.) were used for the enantioselective esterification reaction of (R,S)-ibuprofen with 1-propanol and 2-propanol in saturated cyclohexane as reaction medium. All tested lipases preferentially catalysed the esterification of the S-enantiomer of ibuprofen. However, each one of the analysed lipases demonstrated differences in the catalytic activity. Lipase OF showed the highest conversion degree, and the best enantioselectivity was observed for MY and CRL lipases. The influence of temperature, reaction time and addition of N,N’- dicyclohexylcarbodiimide (DCC) on the enantioselectivity and on the conversion degree in the enzymatic esterification was studied and the optimal condition for nantioselective esterification was evaluated. Moreover, the application of new commercial cellulose-based tris(3,5-dimethylphenylcarbamate) HPLC chiral column was demonstrated for effective separation, qualification and quantification of both substrates and products within one chromatographic analysis